Compositions of autophagy modulating agents and uses thereof

Abstract

The present disclosure is directed to compositions and methods for modulating autophagy for treatment and prevention of autophagy-associated diseases, disorders, or conditions. Methods include administering a pharmaceutical composition comprising an autophagy modulating agent selected from formulas as defined herein.

What is claimed is: 
     
         1 . A method of modulating autophagy in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising an autophagy modulating agent selected from
 the group consisting of:   
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, tautomer, stereoisomer, or analog thereof. 
       
     
     
         2 . The method of  claim 1 , wherein the subject has or is suspected of having an autophagy-associated disease, disorder, or condition. 
     
     
         3 . The method of  claim 2 , wherein the autophagy-associated disease, disorder, or condition is alpha-1 antitrypsin deficiency (ATD). 
     
     
         4 . The method of  claim 2 , wherein the autophagy-associated disease, disorder, or condition is liver disease from alpha-1-antitrypsin deficiency (ATD). 
     
     
         5 . The method of  claim 2 , wherein the autophagy-associated disease, disorder, or condition is Alzheimer's disease (AD). 
     
     
         6 . The method of  claim 2 , wherein the autophagy-associated disease, disorder, or condition is diabetes. 
     
     
         7 . The method of  claim 2 , wherein the autophagy-associated disease, disorder, or condition is Huntington's disease (HD). 
     
     
         8 . The method of  claim 2 , wherein the autophagy-associated disease, disorder, or condition is cancer. 
     
     
         9 . The method of  claim 1 , wherein the therapeutically effective amount of the pharmaceutical composition comprising the autophagy modulating agent reduces aggregated ATZ protein in the subject having α1-antitrypsin deficiency (ATD). 
     
     
         10 . The method of  claim 1 , wherein the therapeutically effective amount of the pharmaceutical composition comprising the autophagy modulating agent reduces cellular accumulation of misfolded aggregated α1-antitrypsin Z variant (ATZ). 
     
     
         11 . The method of  claim 1 , wherein the therapeutically effective amount of the pharmaceutical composition comprising the autophagy modulating agent reduces cellular accumulation of misfolded or aggregated proteins. 
     
     
         12 . The method of  claim 1 , wherein the therapeutically effective amount of the pharmaceutical composition comprising the autophagy modulating agent has anti-tumor activity in the subject having cancer. 
     
     
         13 . The method of  claim 1 , wherein the therapeutically effective amount of the pharmaceutical composition comprising the autophagy modulating agent reduces neuronal cell death. 
     
     
         14 . The method of  claim 1 , wherein the therapeutically effective amount of the pharmaceutical composition comprising the autophagy modulating agent treats hepatic fibrosis. 
     
     
         15 . The method of  claim 1 , wherein the therapeutically effective amount of the pharmaceutical composition comprising the autophagy modulating agent reduces accumulation of misfolded protein in liver cells, liver damage, liver fibrosis, or liver failure. 
     
     
         16 . The method of  claim 1 , wherein the therapeutically effective amount of the pharmaceutical composition comprising the autophagy modulating agent reduces liver fibrosis. 
     
     
         17 . The method of  claim 1 , wherein the therapeutically effective amount of the pharmaceutical composition comprising the autophagy modulating agent does not affect insulin secretion.